Pediatric EBV-negative monomorphic post–solid organ transplant lymphoproliferative disorders [EBV(-)M-PTLD]: Characteristics, treatment, and outcome from 11 pediatric academic centers.
Authors: Zeinab A.M. Afify, Mary Taj, Kavitha Srivatsa, Tamara P. Miller, Holly Edington, Mansi Dalal, Joanna Robles, James Ford, Matthew J. Ehrhardt, Tonya. Ureda, Jeremy Rubinstein, Sarah McCormack, Julia M. Rivers, Karen M. Chisholm, Madison. Kavanaugh, Andrew J. Bukowinski, Erika Friehling, Lianna Marks, Christine Moore Smith, Clinton Mason
Journal: Journal of Clinical Oncology (2022)

10012 Background: Pediatric EBV(-)M-PTLD comprises &lt; 15% of M-PTLD. Two-year-overall survival of pediatric EBV(+) PTLD is 83%. No large multi-institution pediatric-specific reports are available for EBV(-)M-PTLD. Methods: Retrospective study of characteristics, treatment, and outcome of pediatric solid organ recipients diagnosed with EBV(-)M-PTLD at age ≤21 years (y) in 11 pediatric transplant centers in US and UK. Results: Thirty-three patients transplanted with solid organs between 1991-2017 developed EBV(-)M-PTLD. Twenty-two (66%) were male. Median age (range) at organ transplantation was 2.6y(0.1-17), diagnosis of EBV(-)M-PTLD 14y(3-20), interval from transplant to PTLD 8.3y (2.3-18). Transplanted organs were heart (n = 10), kidney (n = 17), liver (n = 4), small bowel (n = 1), liver and small bowel (n = 1). Immunosuppressive therapy at the time of diagnosis of PTLD was available on 31 patients. All were receiving a calcineurin inhibitor except one who was on sirolimus alone. Tacrolimus was given in 27 patients, alone (n = 3), or in various combination with mycophenolate (n = 8), azathioprine (n = 9), prednisone (n = 8), or everolimus (n = 1). Four of these receiving tacrolimus received 3 immunosuppressive drug combinations. Cyclosporine was given in 3 patients, with mycophenolate (n = 1), prednisone (n = 1), or both (n = 2). Murphy stages were I (n = 1), II (n = 7), III (n = 22), and IV (n = 3). Lactate dehydrogenase was elevated in 19/31 (61%) and &gt; 2X upper limit of normal in 10/31 (32%) tested. Pathological diagnoses were diffuse large B-cell lymphoma (n = 30) and B-NHL NOS (n = 3). Treatment included: rituximab alone (n = 1), low-dose cyclophosphamide, prednisone, and rituximab (CPR; n = 9), pediatric mature B-NHL-specific regimen [FAB/LMB with (n = 12) or without (n = 1) rituximab], EPOCH-R (n = 2), R-CHOP (n = 3), modified R-CHOP (n = 2), COP (n = 1), and R-COP (n = 2). At a median 2.9y (0.3-11y) from diagnosis, 26/33 (79%) were alive and in complete remission (CR). Three experienced relapses at 1, 3, and 6.5y after CPR, rituximab alone, and B-NHL therapy, respectively. All achieved a sustained second CR with additional B-NHL therapy. Of the 7 deaths: 6 were from progressive disease despite escalation to intensive B-NHL therapy following initial COP (n = 1), R-COP (n = 1), CPR (n = 2), and B-NHL therapy (n = 2), and one cardiac transplant recipient from presumed cardiotoxicity. There was one graft rejection that was successfully treated. Conclusions: This collaboration represents the first multi-institution series of pediatric EBV(-)M-PTLD. Overall survival was comparable to that reported for pediatric EBV(+) PTLD, but inferior to DLBCL in immunocompetent children. These preliminary data reflect a wide range of therapeutic regimens used over 20 years and strongly support an organized collaborative effort to collect data prospectively.